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Alleviation effects of Bifidobacterium breve on DSS-induced colitis depends on intestinal tract barrier maintenance and gut microbiota modulation

Abstract

Purpose

The study aimed to investigate the discrepancy and potential mechanisms of different CLA-producing B. breve on dextran sulphate sodium (DSS)-induced colitis.

Methods

Colitis was induced in C57BL/6 J mice using DSS. Disease activity index (DAI), histopathological changes, epithelial barrier integrity and epithelial apoptosis were determined. Gut microbiota were gauged to evaluate the systemic effects of CLA-producing B. breve.

Results

Oral administration of different B. breve showed different effects, in which B. breve M1 and B. breve M2 alleviated the inflammation induced by DSS as well as significantly increased the concentration of mucin2 (MUC2) and goblet cells, but neither B. breve M3 nor B. breve M4 had those protective effects. Meanwhile, B. breve M1 and B. breve M2 treatments significantly up-regulated the tight junction (TJ) proteins and ameliorated the epithelial apoptosis lead by DSS challenge. Moreover, inflammatory cytokines (TNF-α, IL-6) were modulated by B. breve M1 and B. breve M2, neither B. breve M3 nor B. breve M4. Furthermore, B. breve M1 and B. breve M2 reduced the abundance of Bacteroides and increased the abundance of Odoribacter, then rebalanced the damaged gut microbiota. Colonic CLA concentrations in mice fed with B. breve M1, B. breve M2, B. breve M3 and B. breve M4 decreased successively, which showed significant positive correlation with the effectiveness of relieving colitis.

Conclusions

Bifidobacterium breve M1 and B. breve M2 alleviated DSS-induced colitis by producing CLA, inhibiting the inflammatory cytokines, maintaining of the intestinal epithelial barrier and regulating the gut microbiota.

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Abbreviations

IBD:

Inflammatory bowel disease

UC:

Ulcerative colitis

DAI:

Disease activity index

CLA:

Conjugated linoleic acid

H&E:

Haematoxylin and Eosin

MPO:

Myeloperoxidase

COX-2:

Cyclooxygenase 2

iNOS:

Inducible nitric oxide synthase

SOD:

Superoxide dismutase

MDA:

Malonic dialdehyde

CAT:

Catalase

GSH-PX:

Glutathione peroxidase

TJ:

Tight junction

MUC2:

Mucin2

AJ:

Adheres junction

References

  1. 1.

    Molodecky NA, Soon S, Rabi DM, Ghali WA, Ferris M, Chernoff G et al (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142:46–54

    PubMed  Google Scholar 

  2. 2.

    Sairenji T, Collins KL, Evans DV (2017) An update on inflammatory bowel disease. Prim Care 44:673–692

    PubMed  Google Scholar 

  3. 3.

    Hanauer SB (2006) Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 12:S3–S9

    PubMed  Google Scholar 

  4. 4.

    Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF (2017) Ulcerative colitis. Lancet 389:1756–1770

    Google Scholar 

  5. 5.

    Green JR, Lobo AJ, Holdsworth CD, Leicester RJ, Gibson JA, Kerr GD et al (1998) Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. Gastroenterology 114:15–22

    CAS  PubMed  Google Scholar 

  6. 6.

    Pearson C (2004) Inflammatory bowel disease. Clin Adv Nutr 100:86–90

    Google Scholar 

  7. 7.

    Osman N, Adawi D, Molin G, Ahrne S, Berggren A, Jeppsson B (2006) Bifidobacterium infantis strains with and without a combination of oligofructose and inulin (OFI) attenuate inflammation in DSS-induced colitis in rats. BMC Gastroenterol 6:6–31

    Google Scholar 

  8. 8.

    Bassaganya-Riera J, Hontecillas R (2006) CLA and n-3 PUFA differentially modulate clinical activity and colonic PPAR-responsive gene expression in a pig model of experimental IBD. Clin Nutr 25:454–465

    CAS  PubMed  Google Scholar 

  9. 9.

    Bassaganya-Riera J, Reynolds K, Martino-Catt S, Cui Y, Hennighausen L, Gonzalez F (2004) Hontecillas, Activation of PPAR [gamma] and [delta] by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Gastroenterology 127:777–791

    CAS  PubMed  Google Scholar 

  10. 10.

    Clément L, Poirier H, Niot I, Bocher V, Guerre-Millo M, Krief S et al (2002) Dietary trans-10, cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. J Lipid Res 43:1400–1409

    PubMed  Google Scholar 

  11. 11.

    Kelley DS, Bartolini GL, Warren JM, Simon VA, Mackey BE, Erickson KL (2004) Contrasting effects of t10, c12- and c9, t11-conjugated linoleic acid isomers on the fatty acid profiles of mouse liver lipids. Lipids 39:135–141

    CAS  PubMed  Google Scholar 

  12. 12.

    Jaudszus A, Moeckel P, Hamelmann E, Jahreis G (2010) Trans-10, cis-12-CLA-caused lipodystrophy is associated with profound changes of fatty acid profiles of liver, white adipose tissue and erythrocytes in mice: possible link to tissue-specific alterations of fatty acid desaturation. Ann Nutr Metab 57:103–111

    CAS  PubMed  Google Scholar 

  13. 13.

    Takahashi Y, Kushiro M, Shinohara K, Ide T (2003) Activity and mRNA levels of enzymes involved in hepatic fatty acid synthesis and oxidation in mice fed conjugated linoleic acid. BBA-Mol Cell Biol L 1631:265–273

    CAS  Google Scholar 

  14. 14.

    Rasooly R, Kelley DS, Greg J, Mackey BE, Belury MA, Belury MA et al (2007) Dietary trans 10, cis 12-conjugated linoleic acid reduces the expression of fatty acid oxidation and drug detoxification enzymes in mouse liver. Brit J Nutr 97:58–66

    CAS  PubMed  Google Scholar 

  15. 15.

    Coakley M, Ross RP, Nordgren M, Fitzgerald G, Devery R, Stanton C (2003) Conjugated linoleic acid biosynthesis by human-derived Bifidobacterium species. J Appl Microbiol 94:138–145

    CAS  PubMed  Google Scholar 

  16. 16.

    Chung SH, Kim IH, Park HG, Kang HS, Yoon CS, Jeong HY et al (2008) Synthesis of conjugated linoleic acid by human-derived Bifidobacterium breve LMC 017: utilization as a functional starter culture for milk fermentation. J Agric Food Chem 56:3311–3316

    CAS  PubMed  Google Scholar 

  17. 17.

    Kepler CR, Tucker WP, Tove SB (1971) Biohydrogenation of unsaturated fatty acids. V. Stereospecificity of proton addition and mechanism of action of linoleic acid Δ12-cis, Δ11-trans-isomerase from Butyrivibrio fibrisolvens. J Biol Chem 246:2765–2771

    CAS  PubMed  Google Scholar 

  18. 18.

    Raimondi S, Amaretti A, Leonardi A, Quartieri A, Gozzoli C, Rossi M (2016) Conjugated linoleic acid production by bifidobacteria: screening, kinetic, and composition. Biomed Res Int 2016:1–9

    Google Scholar 

  19. 19.

    Wang J, Chen H, Yang B, Gu Z, Zhang H, Chen W et al (2016) Lactobacillus plantarum ZS2058 produces CLA to ameliorate DSS-induced acute colitis in mice. RSC Adv 6:14457–14464

    CAS  Google Scholar 

  20. 20.

    Yang B, Chen H, Gao H, Wang J, Stanton C, Ross RP et al (2018) Bifidobacterium breve CCFM683 could ameliorate DSS-induced colitis in mice primarily via conjugated linoleic acid production and gut microbiota modulation. J Funct Foods 49:61–72

    CAS  Google Scholar 

  21. 21.

    Yang B, Chen H, Gu Z, Tian F, Ross RP, Stanton C et al (2014) Synthesis of conjugated linoleic acid by the linoleate isomerase complex in food-derived lactobacilli. J Appl Microbiol 117:430–439

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Fang Z, Li L, Liu X, Lu W, Zhao J, Zhang H et al (2019) Strain-specific ameliorating effect of Bifidobacterium longum on atopic dermatitis in mice. J Funct Foods 60:103426

    CAS  Google Scholar 

  23. 23.

    Mennigen R, Nolte K, Rijcken E, Utech M, Loeffler B, Senninger N et al (2009) Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am J Physiol-Gastr L 296:G1140–G1149

    CAS  Google Scholar 

  24. 24.

    Murthy SNS, Cooper HS, Shim H, Shah RS, Ibrahim SA, Sedergran DJ (1993) Treatment of dextran sulfate sodium-induced murine colitis by intra colonic cyclosporine. Digest Dis Sci 38:1722–1734

    CAS  PubMed  Google Scholar 

  25. 25.

    Rees V (1998) Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 114:385–391

    PubMed  Google Scholar 

  26. 26.

    Steedman HF (1950) Alcian blue 8GS: a new stain for mucin. J Cell Sci 91:477–479

    CAS  Google Scholar 

  27. 27.

    Wu H, Ye L, Lu X, Xie S, Yang Q, Yu Q (2018) Lactobacillus acidophilus alleviated Salmonella-induced goblet cells loss and colitis by Notch pathway. Mol Nutr Food Res 62:1800552

    Google Scholar 

  28. 28.

    Tan GX, Wang XN, Tang YY, Cen WJ, Li ZH, Wang GC et al (2019) PP22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma cell line CNE-2 by inducing endoplasmic reticulum stress, down regulating STAT3 signaling, and modulating the MAPK pathway. J Cell Physiol 234:2618–2630

    CAS  PubMed  Google Scholar 

  29. 29.

    Classics Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917

    Google Scholar 

  30. 30.

    Schwenke DC (2002) Alpha-tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits. J Lipid Res 43:1927–1938

    CAS  PubMed  Google Scholar 

  31. 31.

    Yang Q, Wang S, Ji Y, Chen H, Zhang H, Chen W et al (2017) Dietary intake of n-3 PUFAs modifies the absorption, distribution and bioavailability of fatty acids in the mouse gastrointestinal tract. Lipids Health Dis 16:10

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Yan S, Yang B, Zhao J, Zhao J, Stanton C, Ross RP et al (2019) A ropy exopolysaccharide producing strain Bifidobacterium longum subsp. longum YS108R alleviates DSS-induced colitis by maintenance of the mucosal barrier and gut microbiota modulation. Food Funct 10:1595–1608

    CAS  PubMed  Google Scholar 

  33. 33.

    Chassaing B, Aitken JD, Malleshappa M, Vijay-Kumar M (2014) Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol 104:15–25

    PubMed  Google Scholar 

  34. 34.

    Zwolinska-Wcislo M, Brzozowski T, Ptak-Belowska A, Targosz A, Urbanczyk K, Kwiecien S et al (2011) Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis. World J Gastroenterol 17:4076–4089

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Xing J, You C, Dong K, Sun J, You H, Dong Y et al (2013) Ameliorative effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis and their mechanisms in rats. Int Immunopharmacol 15:524–531

    CAS  PubMed  Google Scholar 

  36. 36.

    Peterson LW, Artis D (2014) Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol 14:141–153

    CAS  PubMed  Google Scholar 

  37. 37.

    Kim YS, Ho SB (2010) Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep 12:319–330

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Hansson GC (2012) Role of mucus layers in gut infection and inflammation. Curr Opin Microbio 15:57–62

    CAS  Google Scholar 

  39. 39.

    Van Klinken BJ, Van der Wal JW, Einerhand AW, Buller HA, Dekker J (1999) Sulphation and secretion of the predominant secretory human colonic mucin MUC2 in ulcerative colitis. Gut 44:387–393

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    Theodoratou E, Campbell H, Ventham NT, Kolarich D, Pucic-Bakovic M, Zoldos V et al (2014) The role of glycosylation in IBD. Nat Rev Gastroenterol Hepatol 11:588–600

    CAS  PubMed  Google Scholar 

  41. 41.

    Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ et al (1999) Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology 116:301–309

    CAS  PubMed  Google Scholar 

  42. 42.

    Shen L, Weber CR, Raleigh DR, Yu D, Turner JR (2011) Tight junction pore and leak pathways: a dynamic duo. Annu Rev Physiol 73:283–309

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Ivanov AI, Naydenov NG (2013) Dynamics and regulation of epithelial adherens junctions: recent discoveries and controversies. Int Rev Cell Mol Biol 303:27–99

    CAS  PubMed  Google Scholar 

  44. 44.

    Ivanov AI, Parkos CA, Nusrat A (2010) Cytoskeletal regulation of epithelial barrier function during inflammation. Am J Pathol 177:512–524

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Zakostelska Z, Kverka M, Klimesova K, Rossmann P, Mrazek J, Kopecny J et al (2011) Lysate of probiotic Lactobacillus casei DN-114 001 ameliorates colitis by strengthening the gut barrier function and changing the gut microenvironment. PLoS ONE 6:e27961

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Srutkova D, Schwarzer M, Hudcovic T, Zakostelska Z, Drab V, Spanova A et al (2015) Bifidobacterium longum CCM 7952 promotes epithelial barrier function and prevents acute DSS-induced colitis in strictly strain-specific manner. PLoS ONE 10:e0134050

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Wang G, Xu Q, Jin X, Hang F, Liu Z, Zhao J et al (2018) Effects of lactobacilli with different regulatory behaviours on tight junctions in mice with dextran sodium sulphate-induced colitis. J Funct Foods 47:107–115

    CAS  Google Scholar 

  48. 48.

    Liu HY, Roos S, Jonsson H, Ahl D, Dicksved J, Lindberg JE et al (2015) Effects of lactobacillus johnsonii and lactobacillus reuteri on gut barrier function and heat shock proteins in intestinal porcine epithelial cells. Physiol Rep 3:e12355

    PubMed  PubMed Central  Google Scholar 

  49. 49.

    Fei L, Xu K (2016) Zhikang Capsule ameliorates dextran sodium sulfate-induced colitis by inhibition of inflammation, apoptosis, oxidative stress and MyD88-dependent TLR4 signaling pathway. J Ethnopharmacol 192:236–247

    PubMed  Google Scholar 

  50. 50.

    Hegazy SK (2010) Effect of probiotics on pro-inflammatory cytokines and NF-κB activation in ulcerative colitis. World J Gastroenterol 16:4145–4151

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Horiuchi T, Mitoma H, Harashima S, Tsukamoto H, Shimoda T (2010) Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford) 49:1215–1228

    CAS  Google Scholar 

  52. 52.

    Lee IA, Bae EA, Lee JH, Lee H, Ahn YT, Huh CS et al (2010) Bifidobacterium longum HY8004 attenuates TNBS-induced colitis by inhibiting lipid peroxidation in mice. Inflamm Res 59:359–368

    CAS  PubMed  Google Scholar 

  53. 53.

    Jin S, Zhao D, Cai C, Song D, Shen J, Xu A et al (2017) Low-dose penicillin exposure in early life decreases Th17 and the susceptibility to DSS colitis in mice through gut microbiota modification. Sci Rep 7:43662

    PubMed  PubMed Central  Google Scholar 

  54. 54.

    Fujio-Vejar S, Vasquez Y, Morales P, Magne F, Vera-Wolf P, Ugalde JA et al (2017) The gut microbiota of healthy Chilean subjects reveals a high abundance of the phylum Verrucomicrobia. Front Microbiol 8:1–11

    Google Scholar 

  55. 55.

    Torres PJ, Siakowska M, Banaszewska B, Pawelczyk L, Duleba AJ, Kelley ST et al (2018) Gut microbial diversity in women with polycystic ovary syndrome correlates with hyperandrogenism. J Clin Endocr Metab 103:1502–1511

    PubMed  Google Scholar 

  56. 56.

    Gomez-Arango LF, Barrett H, McIntyre D, Callaway LK, Morrison M, Nitert MD (2016) Increased systolic and diastolic blood pressure is associated with altered gut microbiota composition and butyrate production in early pregnancy. Hypertension 68:974–977

    CAS  PubMed  Google Scholar 

  57. 57.

    Chen G, Ran X, Li B, Li Y, He D, Huang B et al (2018) Sodium butyrate inhibits inflammation and maintains epithelium barrier integrity in a TNBS-induced inflammatory bowel disease mice model. EBioMedicine 30:317–325

    PubMed  PubMed Central  Google Scholar 

  58. 58.

    Chen L, Sun M, Wu W, Yang W, Huang X, Xiao Y (2019) Microbiota metabolite butyrate differentially regulates Th1 and Th17 cells’ differentiation and function in induction of colitis. Inflamm Bowel Dis 25:1450–1461

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Kuwahara T, Yamashita A, Hirakawa H, Nakayama H, Toh H, Okada N et al (2004) Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions regulating cell surface adaptation. Proc Natl Acad Sci 101:14919–14924

    CAS  PubMed  Google Scholar 

  60. 60.

    Setoyama H, Imaoka A, Ishikawa H, Umesaki Y (2003) Prevention of gut inflammation by Bifidobacterium in dextran sulfate-treated gnotobiotic mice associated with Bacteroides strains isolated from ulcerative colitis patients. Microbes Infect 5:115–122

    PubMed  Google Scholar 

  61. 61.

    Bamba T, Matsuda H, Endo M, Fujiyama Y (1995) The pathogenic role of Bacteroides vulgatus in patients with ulcerative colitis. J Gastroenterol 30:45–47

    PubMed  Google Scholar 

  62. 62.

    Hudcovic T, Kozakova H, Kolinska J, Stepankova R, Hrncir T, Tlaskalova- Hogenova H (2009) Monocolonization with Bacteroides ovatus protects immu-nodeficient SCID mice from mortality in chronic intestinal inflammation caused by long-lasting dextran sodium sulfate treatment. Physiol Res 58:101–110

    CAS  PubMed  Google Scholar 

  63. 63.

    Borniquel S, Jadert C, Lundberg JO (2012) Dietary conjugated linoleic acid activates PPARgamma and the intestinal trefoil factor in SW480 cells and mice with dextran sulfate sodium-induced colitis. J Nutr 142:2135–2140

    CAS  PubMed  Google Scholar 

  64. 64.

    Bassaganya-Riera J, Viladomiu M, Pedragosa M, De Simone C, Carbo A, Shaykhutdinov R et al (2012) Probiotic bacteria produce conjugated linoleic acid locally in the gut that targets macrophage PPAR gamma to suppress colitis. PLoS ONE 7:e31238

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Chen Y, Yang B, Ross RP, Jin Y, Stanton C, Zhao J et al (2019) Orally administered CLA ameliorates DSS-induced colitis in mice via intestinal barrier improvement, oxidative stress reduction, and inflammatory cytokine and gut microbiota modulation. J Agric Food Chem 67:13282–13298

    CAS  Google Scholar 

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Acknowledgements

This research was supported by the National Natural Science Foundation of China (Nos. 31801521, 31722041, 31820103010), National First-Class Discipline Program of Food Science and Technology (JUFSTR20180102), the Fundamental Research Funds for the Central Universities (JUSRP52003B), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX19_1829), Wuxi Young Talent Foundation (QNRC075) and the Jiangsu Province “Collaborative Innovation Center for Food Safety and Quality Control”.

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YC performed the experiments and analysed the data. BY, YJ, HZ and WC provided intellectual inputs and designed the experiments. JXZ contributed to the data acquisition. RPR and CS critically reviewed the manuscript. YC and BY wrote the manuscript. BY, YJ, RPR and CS revised the manuscript.

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Correspondence to Yan Jin or Bo Yang.

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The authors declare no conflict of interest.

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Chen, Y., Jin, Y., Stanton, C. et al. Alleviation effects of Bifidobacterium breve on DSS-induced colitis depends on intestinal tract barrier maintenance and gut microbiota modulation. Eur J Nutr 60, 369–387 (2021). https://doi.org/10.1007/s00394-020-02252-x

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Keywords

  • Bifidobacterium breve
  • Conjugated linoleic acid
  • Colitis
  • Intestinal tract barrier
  • Gut microbiota